Kaposi's sarcoma is a form of malignancy which has particular significance as an opportunistic condition suffered by HIV-infected individuals. It is also seen in individuals who are immunosuppressed for other reasons, such as in transplant recipients.
The nature of the pathology and the origin of the involved cells in Kaposi's sarcoma is not completely understood. It is, however, believed that this is a multi-focal vascular lesion. The frequent association with clinical states characterized by alterations in immune function have led to the postulation that endothelial cells are the cells of origin, but the tumor cells do not have all the immunohistochemical characteristics of vascular endothelia. It has therefore been postulated that the origin is a mesenchymal cell, possibly a lymphatic endothelial cell. Kaposi's sarcoma-derived cell lines are, however, available for study.
A number of treatments have been proposed for Kaposi's sarcoma, including the administration of isotretinoin (13-cis-retinoic acid), a vitamin A analog which is thought to be effective because of its known potentiation of the T-cell immune response and inhibition of virus induction (Ziegler, J., et al. The Lancet, Sep. 15, 1984:641). Application has been made for patent coverage of methods to treat Kaposi's sarcoma using the oxide forms of retinene such as cis or trans retinol, retinal, or retonic acid, in combination with an oxidized oil by Dietlin, F., et al., French application no. 2645747, published 19 Oct. 1990. Platelet factor 4 (PF4) and its related peptides have been proposed as a treatment on the basis of the ability of the recombinantly produced factor to inhibit blood vessel proliferation in the chicken chorioallantoic membrane (Maione, T. E., et al. Science (1990) 247:77-79; Sharpe, R. J., et al. J N C I (1990) 82:848-852).
IL-6 is a cytokine which is known to exhibit a number of functions, including regulation of the differentiation of activated and mature B-cell stages. This cytokine also regulates growth and immunoglobulin secretion by Epstein Barr virus transformed B-cell lines and seems to be essential for mitogen-stimulated B lymphocytes to become immunoglobulin-secreting cells. Brieva, J. A., et al. Cellular Immunol (1990) 130:303-310 showed that absent IL-6, most lymphoblastoid B-cells failed to mature to the level of secreting antibody. In addition, it is known that HIV infection elevates the levels of IL-6 in human subjects (Nakajima, K., et al. J Immunol (1989) 142:531-536; Breen, E. C., et al., J Immunol (1990) 144:480-484).
It has now been found that IL-6 appears to be an autocrine growth factor for AIDS-derived Kaposi sarcoma cells (AIDS-KS cells). This work was published by Miles, S. A., et al., Proc Natl Acad Sci USA (1990) 87:4068-4072 which was mailed to subscribers 31 May 1990, and is incorporated herein by reference in its entirety. By virtue of this discovery, the design of agents for the control or treatment of Kaposi's sarcoma that interfere with the action of IL-6 on these cells has been made possible.